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Conditional deletion of nonmuscle myosin II-A in mouse tongue epithelium results in squamous cell carcinoma

机译:有条件地删除小鼠舌上皮中非肌肉肌球蛋白II-A导致鳞状细胞癌

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摘要

To investigate the contribution of nonmuscle myosin II-A (NM II-A) to early cardiac development we crossed Myh9 floxed mice and Nkx2.5 cre-recombinase mice. Nkx2.5 is expressed in the early heart (E7.5) and later in the tongue epithelium. Mice homozygous for deletion of NM II-A (ANkx/ANkx) are born at the expected ratio with normal hearts, but consistently develop an invasive squamous cell carcinoma (SCC) of the tongue (32/32 ANkx/ANkx) as early as E17.5. To assess reproducibility a second, independent line of Myh9 floxed mice derived from a different embryonic stem cell clone was tested. This second line also develops SCC indistinguishable from the first (15/15). In ANkx/ANkx mouse tongue epithelium, genetic deletion of NM II-A does not affect stabilization of TP53, unlike a previous report for SCC. We attribute the consistent, early formation of SCC with high penetrance to the role of NM II in maintaining mitotic stability during karyokinesis.
机译:为了研究非肌肉肌球蛋白II-A(NM II-A)对早期心脏发育的贡献,我们将Myh9荷叶小鼠和Nkx2.5 cre-重组酶小鼠杂交。 Nkx2.5在早期心脏(E7.5)中表达,然后在舌头上皮中表达。纯净的NM II-A(A Nkx / A Nkx )缺失的小鼠与正常心脏相比以预期的比例出生,但是持续发展为浸润性鳞状细胞癌(SCC) )(32/32 A Nkx / A Nkx )早于E17.5。为了评估可重复性,测试了来自不同胚胎干细胞克隆的第二条独立的Myh9 floxed小鼠品系。这第二条线也使SCC与第一条线(15/15)没有区别。在A Nkx / A Nkx 小鼠舌头上皮细胞中,NM II-A的基因缺失不会影响TP53的稳定,这与先前关于SCC的报道不同。我们将高渗透率的SCC的持续早期形成归因于NM II在核运动期间维持有丝分裂稳定性的作用。

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